Human herpesvirus 6 (HHV-6) comprises two viral species, HHV-6A and HHV-6B, closely related but differing for pathogenic and biological characteristics. Both viral species are predominantly lymphotropic, infecting T lymphocytes and other lymphoid cells, including natural killer (NK) cells. The interactions between HHV-6 and NK cells have been scarcely studied, but it has become clear that NK cells are not only crucial in immune protection during the early phases of infection, but also that HHV-6 infection can affect NK cell functions. In this report, we shortly summarize the interactions between HHV-6 and NK cells.